Existing treatments for androgenetic alopecia (AGA) are unsatisfactory, owing to the two major reasons: (1) Oxidative stress and vascularization deficiency in the perifollicular microenvironment provoke the premature senescence of hair follicles, limiting the transformation of hair growth cycle from the telogen to the anagen phase
(2) The amount of drug delivered to the perifollicular region located in the deep dermis is very limited for passive drug delivery systems. Herein, we developed a gas-propelled microneedle patch integrated with ferrum-chelated puerarin/quercetin nanoparticles (PQFN) to increase drug accumulation in hair follicles and reshape the perifollicular microenvironment for improved hair-regenerating effects. PQFN can rejuvenate testosterone (Tes)-induced senescence of dermal papilla cells by scavenging ROS, restoring mitochondrial function, regulating signaling pathways related to hair regeneration, and upregulating hair growth-promoting genes. PQFN more efficiently promoted endothelial cell proliferation, migration, and tube formation than ferrum-chelated quercetin nanoparticles (QFN) because of puerarin's proangiogenic effects. Compared with passive MNs, gas-propelled MNs promoted drug diffusion and permeation into deeper skin layers, resulting in significantly higher drug accumulation in hair follicles. Pharmacodynamic studies on an AGA mouse model further showed that PQFN-loaded active MNs achieved higher hair coverage by alleviating oxidative stress, promoting angiogenesis, and rejuvenating senescent cells. Therefore, this study presents a novel "anti-hair follicle aging" treatment strategy for AGA.